In this proposal I describe a system for the experimental analysis of the circuitry for gene regulation in Drosophila by the investigation of mutations in the enzyme alcohol dehydrogenase (ADH). We have focused on this gene product because it is a relatively simple protein; because it is isolatable in large quantities; because it appears to be unessential for survival under most conditions; because it shows interesting tissue specificities and developmental changes; and because mutations, revertants, and recombinants at the ADH locus are detectable by chemical procedures which are capable of screening extremely large numbers of individuals. Five distinct sub-proposals are presented. In the first, I propose to continue working to generate a large number of mutations in ADH. Secondly, my laboratory will characterize these mutants by a variety of techniques. Thirdly, we will decide whether these mutations are in the ADH structural locus by virtue of their intracistronic map position, and by virtue of changes in their peptide composition. Fourthly, we will try to generate "transregulatory" mutants in which the regulatory elements of one gene will control the structural locus of ADH. Finally, we will look for supressors of ADH-negatives in an effort to further describe the nature of regulatory loci.